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We demonstrate the use of Stimulated Emission Depletion (STED) spectroscopy to map the electron-optical-phonon sideband of the ground state of the radiative transition of color centers in hexagonal boron nitride emitting at 2.0-2.2 eV, with in-plane linear polarization. The measurements are compared to Photoluminescence of Excitation (PLE) spectra, that maps the electron-optical-phonon sideband of the excited state. The main qualitative difference is a red-shift in the longitudinal optical phonon peak associated with $E_{1u}$ symmetry at the zone center. We argue that this is consistent with recent findings for a carbon-based line defect with admixture of energetically similar excited states.

We report on multicolor excitation experiments with color centers in hexagonal boron nitride at cryogenic temperatures. We demonstrate controllable optical switching between bright and dark states of color centers emitting around 2 eV. Resonant, or quasi-resonant, excitation of photoluminescence also pumps the color center, via a two-photon process, into a dark state, where it becomes trapped. Repumping back into the bright state has a step-like spectrum with a defect-dependent threshold between 2.25 and 2.6 eV. This behavior is consistent with photoionization and charging between optically bright and dark states of the defect. Furthermore, a second zero phonon line, detuned by +0.4 eV, is observed in absorption with orthogonal polarization to the emission, evidencing an additional energy level in the color center.

We report optically detected magnetic resonance (ODMR) measurements of an ensemble of spin-1 negatively charged boron vacancies in hexagonal boron nitride. The photoluminescence decay rates are spin-dependent, with inter-system crossing rates of $1.02~\mathrm{ns^{-1}}$ and $2.03~\mathrm{ns^{-1}}$ for the $m_s=0$ and $m_s=\pm 1$ states, respectively. Time-gating the photoluminescence enhances the ODMR contrast by discriminating between different decay rates. This is particularly effective for detecting the spin of the optically excited state, where a zero-field splitting of $\vert D_{ES}\vert=2.09~\mathrm{GHz}$ is measured. The magnetic field dependence of the time-gated photoluminescence exhibits dips corresponding to the Ground (GSLAC) and excited-state (ESLAC) anti-crossings. Additional dips corresponding to anti-crossings with nearby spin-1/2 parasitic impurities are also observed. The ESLAC dip is sensitive to the angle of the external magnetic field. Comparison to a model suggests that the anti-crossings are mediated by the interaction with nuclear spins, and allow an estimate of the ratio of the spin-dependent relaxation rates from the singlet back into the triplet ground state of $\kappa_0/\kappa_1=0.34$. This work provides important spectroscopic signatures of the boron vacancy, and information on the spin pumping and read-out dynamics.

Room-temperature optically detected magnetic resonance experiments on spin-$\frac{3}{2}$ silicon vacancies in $4H$-SiC are reported. The ${m}_{s}=+\frac{1}{2}\ensuremath{\leftrightarrow}\ensuremath{-}\frac{1}{2}$ transition is accessed using a two-microwave-frequency excitation protocol. The ratio of the Rabi frequencies of the $+\frac{3}{2}\ensuremath{\leftrightarrow}+\frac{1}{2}$ and $+\frac{1}{2}\ensuremath{\leftrightarrow}\ensuremath{-}\frac{1}{2}$ transitions is measured to be $(0.901\ifmmode\pm\else\textpm\fi{}0.013)$. The deviation from $\sqrt{3}/2$ is attributed to small difference in $g$ factor for different magnetic dipole transitions. Whereas a spin-$\frac{1}{2}$ system is characterized by a single-spin lifetime ${T}_{1}$, we experimentally demonstrate that the spin-$\frac{3}{2}$ system has three distinct relaxation modes that can be preferentially excited and detected. The measured relaxation times are $(0.41\ifmmode\pm\else\textpm\fi{}0.02){T}_{\mathrm{slow}}={T}_{d}=(3.3\ifmmode\pm\else\textpm\fi{}0.5){T}_{\mathrm{fast}}$. This differs from the values of ${T}_{p}/3={T}_{d}=2{T}_{f}$ expected for pure dipole (${T}_{p}$), quadrupole (${T}_{d}$), and octupole (${T}_{f}$) relaxation modes, respectively, and implies admixing of the slow dipole and fast octupole relaxation modes.

Microwave-to-optical conversion via ferromagnetic magnons has so far been limited by the optical coupling rates achieved in millimeter-scale whispering-gallery-mode resonators. Toward overcoming this limitation, we propose and demonstrate an open magneto-optical cavity containing a thin film of yttrium iron garnet (YIG). We achieve a 0.1 pL ($100\phantom{\rule{0.2em}{0ex}}\ensuremath{\mu}{\mathrm{m}}^{3}$) optical mode volume, approximately $50$ times smaller than previous devices. From this, we estimate that the magnon single-photon coupling rate is $G\ensuremath{\approx}50$ Hz. This open-cavity design offers the prospect of wavelength-scale mode volumes, small polarization splittings, and good magneto-optical mode overlap. With achievable further improvements and optimization, efficient microwave-optical conversion and magnon cooling devices become a realistic possibility.

Low temperature photoluminescence spectra of a color center in hexagonal boron nitride are analyzed. The acoustic phonon sideband can be described by a deformation coupling proportional to strain to a phonon bath that is effectively two dimensional. The optical phonon band is described by Frohlich coupling to the LO-branches, and a deformation coupling proportional to lattice displacement for the TO-branch. The resonances expressed in the optical band vary from defect to defect, in some emitters, coupling to out-of-plane polarized phonons is reported., 7 pages, 4 figs

We experimentally identify the magnetostatic modes active for Brillouin light scattering in the optical whispering gallery modes of a yttrium iron garnet sphere. Each mode is identified by magnetic field dispersion of ferromagnetic-resonance spectroscopy and coupling strength to the known field distribution of the microwave drive antenna. Our optical measurements confirm recent predictions that higher-order magnetostatic modes can also generate optical scattering, according to the selection rules derived from the axial symmetry. From this we summarize the selection rules for Brillouin light scattering. We give experimental evidence that the optomagnonic coupling to non-uniform magnons can be higher than that of the uniform Kittel mode., 5 pages, 5 figures

We demonstrate that multiply coupled spinor polariton condensates can be optically tuned through a sequence of spin-ordered phases by changing the coupling strength between nearest neighbors. For closed four-condensate chains these phases span from ferromagnetic (FM) to antiferromagnetic (AFM), separated by an unexpected crossover phase. This crossover phase is composed of alternating FM-AFM bonds. For larger eight-condensate chains, we show the critical role of spatial inhomogeneities and demonstrate a scheme to overcome them and prepare any desired spin state. Our observations thus demonstrate a fully controllable nonequilibrium spin lattice., We acknowledge Grants No. EPSRC EP/L027151/1, No. EU INDEX 289968, No. ERC “POLAFLOW” Starting Grant, ERC LINASS 320503, Spanish MEC (MAT2008- 01555), Mexican CONACYT 251808, Leverhulme Trust Grant No. VP1-2013-011 and Fundación La Caixa. H. S. and I. S. acknowledge support by the Research Fund of the University of Iceland, The Icelandic Research Fund, Grant No. 163082-051. T. L. was supported by the MOE AcRF Tier 1 Grant No. 2016-T1-001-084. P. S. acknowledges financial support from the Stavros Niarchos Foundation, “ARCHERS” project.

Domain wall motion driven by ultra-short laser pulses is a pre-requisite for envisaged low-power spintronics combining storage of information in magnetoelectronic devices with high speed and long distance transmission of information encoded in circularly polarized light. Here we demonstrate the conversion of the circular polarization of incident femtosecond laser pulses into inertial displacement of a domain wall in a ferromagnetic semiconductor. In our study, we combine electrical measurements and magneto-optical imaging of the domain wall displacement with micromagnetic simulations. The optical spin-transfer torque acts over a picosecond recombination time of the spin-polarized photo-carriers that only leads to a deformation of the initial domain wall structure. We show that subsequent depinning and micrometre-distance displacement without an applied magnetic field or any other external stimuli can only occur due to the inertia of the domain wall., Domain wall motion driven by ultra-short laser pulses has potential for storage of information in magnetoelectronic devices. Here the authors demonstrate the conversion of a circularly polarized femtosecond laser light into inertial displacement of a domain wall in a ferromagnetic semiconductor.

Deleterious germline variants in CDKN2A account for around 40% of familial melanoma cases1, while rare variants in CDK4, BRCA2, BAP1, and the promoter of TERT, have also been linked to the disease2-5. Here we set out to identify novel high-penetrance susceptibility genes in unexplained cases by sequencing 184 melanoma patients from 105 pedigrees recruited in the United Kingdom, the Netherlands, and Australia that were negative for variants in known predisposition genes. We identify families where melanoma co-segregates with loss-of-function variants in the protection of telomeres 1 (POT1) gene, a proportion of members presenting with an early age of onset and multiple primaries. We show that these variants either affect POT1 mRNA splicing or alter key residues in the highly conserved oligonucleotide-/oligosaccharide-binding (OB) domains of POT1, disrupting protein-telomere binding, leading to increased telomere length. Thus, POT1 variants predispose to melanoma formation via a direct effect on telomeres.

Next-generation sequencing techniques have emerged as powerful tools for the understanding of cancer genomes. In recent years, whole-exome and whole-genome sequencing strategies have enabled the annotation of a comprehensive mutation landscape of chronic lymphocytic leukemia (CLL), the most frequent leukemia in western countries. Several recurrently mutated genes have been identified, with a subset being validated as neoplastic drivers. Still, a main challenge remains for the differentiation between driver and passenger mutations among candidates as well as for the functional description of the newly discovered leukemogenic genes that could be utilized for personalized anti-tumor strategies. In this scenario, we have identified the metabolic enzyme sucrase-isomaltase (SI) as one of the most frequently mutated genes in a cohort of 105 CLL patients. Here, we demonstrate that these SI mutations result in loss of enzyme function by preventing the biosynthesis of catalytically competent SI at the cell surface. Transcriptome analyses of RNA from CLL patients with SI loss-of-function mutations have uncovered gene expression patterns that depict ample metabolic reprogramming, pinpointing SI as a putative player in the cancer-associated metabolic switch. These results highlight SI as a relevant target for clinical evaluation in future CLL studies.

We report spin and intensity coupling of an exciton-polariton condensate to the mechanical vibrations of a circular membrane microcavity. We optically drive the microcavity resonator at the lowest mechanical resonance frequency while creating an optically-trapped spin-polarized polariton condensate in different locations on the microcavity, and observe spin and intensity oscillations of the condensate at the vibration frequency of the resonator. Spin oscillations are induced by vibrational strain driving, whilst the modulation of the optical trap due to the displacement of the membrane causes intensity oscillations in the condensate emission. Our results demonstrate spin-phonon coupling in a macroscopically coherent condensate., 5 pages

Carlos Lopez-Otin and colleagues report recurrent mutations in POT1 in chronic lymphocytic leukemia. This is the first member of the telomeric shelterin complex reported to be mutated in human cancer.

An enhancement in Brillouin light scattering of optical photons with magnons is demonstrated in magneto-optical whispering gallery mode resonators tuned to a triple-resonance point. This occurs when both the input and output optical modes are resonant with those of the whispering gallery resonator, with a separation given by the ferromagnetic resonance frequency. The identification and excitation of specific optical modes allows us to gain a clear understanding of the mode-matching conditions. A selection rule due to wave vector matching leads to an intrinsic single-sideband excitation. Strong suppression of one sideband is essential for one-to-one frequency mapping in coherent optical-to-microwave conversion., Engineering and Physical Sciences Research Council (Grant ID: EP/ M50693X/1), European Research Council (Grant ID: 648613), Hitachi (Research Fellowship), Royal Society (University Research Fellowship), Winton Programme for the Physics of Sustainability, This is the author accepted manuscript. The final version is available from the American Physical Society via https://doi.org/10.1103/PhysRevLett.117.133602

We demonstrate that yttrium iron garnet microspheres support optical whispering gallery modes similar to those in non-magnetic dielectric materials. The direction of the ferromagnetic moment tunes both the resonant frequency via the Voigt effect as well as the degree of polarization rotation via the Faraday effect. An understanding of the magneto-optical coupling in whispering gallery modes, where the propagation direction rotates with respect to the magnetization, is fundamental to the emerging field of cavity optomagnonics., Engineering and Physical Sciences Research Council (Grant IDs: EP/M50693X/1, EP/L027151/1), European Research Council (Grant ID: 648613), Hitachi (research fellowship), Royal Society (University Research Fellowship), Winton programme for the Physics of Sustainability, This is the author accepted manuscript. The final version is available from the American Physical Society via http://dx.doi.org/10.1103/PhysRevA.92.063845

We study optically driven Rabi rotations of a quantum dot exciton transition between 5 and 50 K, and for pulse-areas of up to $14\pi$. In a high driving field regime, the decay of the Rabi rotations is nonmonotonic, and the period decreases with pulse-area and increases with temperature. By comparing the experiments to a weak-coupling model of the exciton-phonon interaction, we demonstrate that the observed renormalization of the Rabi frequency is induced by fluctuations in the bath of longitudinal acoustic phonons, an effect that is a phonon analogy of the Lamb-shift., Comment: 4-pages, 2 figs, final version published in PRL

The extrinsic dephasing of a hole spin confined to a self-assembled quantum dot is dominated by charge noise acting on an electric-field dependent g-factor. Here we propose the use of the optical Stark effect to reduce the sensitivity of the effective hole Zeeman energy to fluctuations in the local electric-field. Calculations using measured quantum dot parameters are presented, and demonstrate a factor of 10-100 reduction in the extrinsic dephasing. Compared to active stabilization methods, this technique should benefit from reduced experimental complexity., Comment: 7 pages, 4 figs, final version

Mitochondria are dynamic subcellular organelles that convert nutrient intermediates into readily available energy equivalents. Optimal mitochondrial function is ensured by a highly evolved quality control system, coordinated by protein machinery that regulates a process of continual fusion and fission. In this work, we provide in vivo evidence that the ATP-independent metalloprotease OMA1 plays an essential role in the proteolytic inactivation of the dynamin-related GTPase OPA1 (optic atrophy 1). We also show that OMA1 deficiency causes a profound perturbation of the mitochondrial fusion–fission equilibrium that has important implications for metabolic homeostasis. Thus, ablation of OMA1 in mice results in marked transcriptional changes in genes of lipid and glucose metabolic pathways and substantial alterations in circulating blood parameters. Additionally, Oma1-mutant mice exhibit an increase in body weight due to increased adipose mass, hepatic steatosis, decreased energy expenditure and impaired thermogenenesis. These alterations are especially significant under metabolic stress conditions, indicating that an intact OMA1-OPA1 system is essential for developing the appropriate adaptive response to different metabolic stressors such as a high-fat diet or cold-shock. This study provides the first description of an unexpected role in energy metabolism for the metalloprotease OMA1 and reinforces the importance of mitochondrial quality control for normal metabolic function.

Aging is a multifactorial process that affects most of the biological functions of the organism and increases susceptibility to disease and death. Recent studies with animal models of accelerated aging have unveiled some mechanisms that also operate in physiological aging. However, little is known about the role of microRNAs (miRNAs) in this process. To address this question, we have analysed miRNA levels in Zmpste24-deficient mice, a model of Hutchinson–Gilford progeria syndrome. We have found that expression of the miR-29 family of miRNAs is markedly upregulated in Zmpste24−/− progeroid mice as well as during normal aging in mouse. Functional analysis revealed that this transcriptional activation of miR-29 is triggered in response to DNA damage and occurs in a p53-dependent manner since p53−/− murine fibroblasts do not increase miR-29 expression upon doxorubicin treatment. We have also found that miR-29 represses Ppm1d phosphatase, which in turn enhances p53 activity. Based on these results, we propose the existence of a novel regulatory circuitry involving miR-29, Ppm1d and p53, which is activated in aging and in response to DNA damage.

A two-photon absorption resonance is observed when the sum-frequency of two laser pulses equals the creation energy of a biexciton in a single InAs/GaAs semiconductor quantum dot. Resonant excitation of the two-color two-photon transition results in a coherent oscillation that is remarkably similar to a single-color two-photon Rabi oscillation of the crystal-ground to biexciton optical transition. A model explaining the coherent two-photon absorption is presented.

A hole spin is a potential solid-state q-bit, that may be more robust against nuclear spin induced dephasing than an electron spin. Here we propose and demonstrate the sequential preparation, control and detection of a single hole spin trapped on a self-assembled InGaAs/GaAs quantum dot. The dot is embedded in a photodiode structure under an applied electric field. Fast, triggered, initialization of a hole spin is achieved by creating a spin-polarized electron–hole pair with a picosecond laser pulse, and in an applied electric field, waiting for the electron to tunnel leaving a spin-polarized hole. Detection of the hole spin with picoseconds time resolution is achieved using a second picosecond laser pulse to probe the positive trion transition, where a trion is created conditional on the hole spin being detected as a change in photocurrent. Finally, using this setup we observe a Rabi rotation of the hole–trion transition that is conditional on the hole spin, which for a pulse area of 2 π can be used to impart a phase shift of π between the hole spin states, a non-general manipulation of the hole spin.

We present a two-colour photocurrent detection method for coherent control of a single InGaAs/GaAs self-assembled quantum dot. A pulse shaping technique provides a high degree of control over picosecond optical pulses. Rabi rotations on the exciton to biexciton transition are presented, and fine structure beating is detected via time-resolved measurements. (© 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Kallikrein-related peptidase 4 (KLK4) is one of the 15 members of the human KLK family and a trypsin-like, prostate cancer-associated serine protease. Signaling initiated by trypsin-like serine proteases are transduced across the plasma membrane primarily by members of the protease-activated receptor (PAR) family of G protein-coupled receptors. Here we show, using Ca(2+) flux assays, that KLK4 signals via both PAR-1 and PAR-2 but not via PAR-4. Dose-response analysis over the enzyme concentration range 0.1-1000 nM indicated that KLK4-induced Ca(2+) mobilization via PAR-1 is more potent than via PAR-2, whereas KLK4 displayed greater efficacy via the latter PAR. We confirmed the specificity of KLK4 signaling via PAR-2 using in vitro protease cleavage assays and anti-phospho-ERK1/2/total ERK1/2 Western blot analysis of PAR-2-overexpressing and small interfering RNA-mediated receptor knockdown cell lines. Consistently, confocal microscopy analyses indicated that KLK4 initiates loss of PAR-2 from the cell surface and receptor internalization. Immunohistochemical analysis indicated the co-expression of agonist and PAR-2 in primary prostate cancer and bone metastases, suggesting that KLK4 signaling via this receptor will have pathological relevance. These data provide insight into KLK4-mediated cell signaling and suggest that signals induced by this enzyme via PARs may be important in prostate cancer.

We study the coherent properties of a two-level system based on the ground state neutral exciton of a single InGaAs self-assembled quantum dot (SAQD) embedded in an n-i-Schottky diode. By using a photocurrent technique, we observe Rabi oscillations of the exciton population for pulse-areas of up to 6π. We perform two pulse quantum interference experiments to deduce the decoherence rate.

The III–V nanowire quantum dots (NWQDs) monolithically grown on silicon substrates, combining the advantages of both one- and zero-dimensional materials, represent one of the most promising technologies for integrating advanced III–V photonic technologies on a silicon microelectronics platform. However, there are great challenges in the fabrication of high-quality III–V NWQDs by a bottom-up approach, that is, growth by the vapor–liquid–solid method, because of the potential contamination caused by external metal catalysts and the various types of interfacial defects introduced by self-catalyzed growth. Here, we report the defect-free self-catalyzed III–V NWQDs, GaAs quantum dots in GaAsP nanowires, on a silicon substrate with pure zinc blende structure for the first time. Well-resolved excitonic emission is observed with a narrow line width. These results pave the way toward on-chip III–V quantum information and photonic devices on silicon platform.

The shelterin complex protects chromosomal ends by regulating how the telomerase complex interacts with telomeres. Following the recent finding in familial melanoma of inactivating germline mutations in POT1, encoding a member of the shelterin complex, we searched for mutations in the other five components of the shelterin complex in melanoma families.Next-generation sequencing techniques were used to screen 510 melanoma families (with unknown genetic etiology) and control cohorts for mutations in shelterin complex encoding genes: ACD, TERF2IP, TERF1, TERF2, and TINF 2. Maximum likelihood and LOD [logarithm (base 10) of odds] analyses were used. Mutation clustering was assessed with χ(2) and Fisher's exact tests. P values under .05 were considered statistically significant (one-tailed with Yates' correction).Six families had mutations in ACD and four families carried TERF2IP variants, which included nonsense mutations in both genes (p.Q320X and p.R364X, respectively) and point mutations that cosegregated with melanoma. Of five distinct mutations in ACD, four clustered in the POT1 binding domain, including p.Q320X. This clustering of novel mutations in the POT1 binding domain of ACD was statistically higher (P = .005) in melanoma probands compared with population control individuals (n = 6785), as were all novel and rare variants in both ACD (P = .040) and TERF2IP (P = .022). Families carrying ACD and TERF2IP mutations were also enriched with other cancer types, suggesting that these variants also predispose to a broader spectrum of cancers than just melanoma. Novel mutations were also observed in TERF1, TERF2, and TINF2, but these were not convincingly associated with melanoma.Our findings add to the growing support for telomere dysregulation as a key process associated with melanoma susceptibility.

We demonstrate a new method to produce a population inversion in an InGaAs quantum dot by quasi-resonant, incoherent excitation within the LA phonon sideband. A maximum exciton population of 0.67 is measured; applications include single photon sources and single QD lasers.

Great progress has recently been achieved in the understanding of the genomic alterations driving chronic lymphocytic leukemia (CLL). Nevertheless, the specific molecular mechanisms governing chromatin remodeling in CLL are unknown. Here we report the genetic and functional characterization of somatic mutations affecting the chromatin remodeler CHD2, one of the most frequently mutated genes in CLL (5.3%) and in monoclonal B lymphocytosis (MBL, 7%), a B-cell expansion that can evolve to CLL. Most of the mutations affecting CHD2, identified by whole-exome sequencing of 456 CLL and 43 MBL patients, are either truncating or affect conserved residues in functional domains, thus supporting a putative role for CHD2 as a tumor suppressor gene. CHD2 mutants show altered nuclear distribution, and a chromodomain helicase DNA binding protein 2 (CHD2) mutant affected in its DNA-binding domain exhibits defective association with active chromatin. Clinicobiological analyses show that most CLL patients carrying CHD2 mutations also present mutated immunoglobulin heavy chain variable region genes (IGHVs), being the most frequently mutated gene in this prognostic subgroup. This is the first study providing functional evidence supporting CHD2 as a cancer driver and opens the way to further studies of the role of this chromatin remodeler in CLL.

We demonstrate optical manipulation of the position of a domain wall in a dilute magnetic semiconductor, GaMnAsP. Two main contributions are identified. Firstly, photocarrier spin exerts a spin transfer torque on the magnetization via the exchange interaction. The direction of the domain wall motion can be controlled using the helicity of the laser. Secondly, the domain wall is attracted to the hot-spot generated by the focused laser. Unlike magnetic field driven domain wall depinning, these mechanisms directly drive domain wall motion, providing an optical tweezer like ability to position and locally probe domain walls., 5 pages, 4 figs, final version improved by referee feedback

We demonstrate a new method to realize the population inversion of a single InGaAs/GaAs quantum dot excited by a laser pulse tuned within the neutral exciton phonon sideband. In contrast to the conventional method of inverting a two-level system by performing coherent Rabi oscillation, the inversion is achieved by rapid thermalization of the optically dressed states via incoherent phonon-assisted relaxation. A maximum exciton population of 0.67±0.06 is measured for a laser tuned 0.83 meV to higher energy. Furthermore, the phonon sideband is mapped using a two-color pump-probe technique, with its spectral form and magnitude in very good agreement with the result of path-integral calculations.

Effective erythropoiesis requires an appropriate supply of iron and mechanisms regulating iron homeostasis and erythropoiesis are intrinsically linked. Iron dysregulation, typified by iron-deficiency anaemia and iron overload, is common in many clinical conditions and impacts the health of up to 30% of the world's population. The proteins transmembrane protease, serine 6 (TMPRSS6; also termed matriptase-2), HFE and transferrin receptor 2 (TFR2) play important and opposing roles in systemic iron homeostasis, by regulating expression of the iron regulatory hormone hepcidin. We have performed a systematic analysis of mice deficient in these three proteins and show that TMPRSS6 predominates over HFE and TFR2 in hepcidin regulation. The phenotype of mice lacking TMPRSS6 and TFR2 is characterized by severe anaemia and extramedullary haematopoiesis in the spleen. Stress erythropoiesis in these mice results in increased expression of the newly identified erythroid iron regulator erythroferrone, which does not appear to overcome the hepcidin overproduction mediated by loss of TMPRSS6. Extended analysis reveals that TFR2 plays an important role in erythroid cells, where it is involved in terminal erythroblast differentiation and the regulation of erythropoietin. In conclusion, we have identified an essential role for TFR2 in erythropoiesis that may provide new targets for the treatment of anaemia.

GaAs provides a versatile platform for developing on-chip integrated quantum-optical circuits. In this paper we review progress in developing spin-photon interfaces, on-chip beam-splitters and coherent single photon sources based on GaAs photonics.

Iron is an essential element required for development and survival of all living organisms. In fetuses, maternofetal iron transfer across the placenta is essential for growth and development. In neonates, efficient intestinal iron absorption is required to scavenge as much iron as possible from the low-iron-content milk. During these periods, efficient iron mobilization is ensured by the downregulation of the iron regulatory hormone hepcidin by as-yet uncharacterized molecular mechanisms. Here we demonstrate that the recently described hepcidin repressor-the serine protease matriptase-2 (encoded by Tmprss6)-is responsible for this repression throughout development, with its deficiency leading to increased hepcidin levels triggering iron deficiency and anemia starting in utero. This result might have implications for a better understanding of iron homeostasis during early development in iron-refractory iron deficiency anemia patients, who present with microcytic anemia caused by hyperhepcidinemia, and of questions about the role of matriptase-2 in human neonates.

Laryngeal squamous cell carcinoma is a frequent and significant cause of morbidity and mortality. Here we explore the biological basis of this aggressive tumour, and identify two cell-cell adhesion genes as recurrently mutated in this malignancy. We first perform exome sequencing of four laryngeal carcinomas and their matched normal tissues. Among the 569 genes found to present somatic mutations, and based on their recurrence or functional relevance in cancer, we select 40 for further validation in 86 additional laryngeal carcinomas. We detect frequent mutations (14 of 90, 15%) in CTNNA2 and CTNNA3-encoding α-catenins. Functional studies reveal an increase in the migration and invasive ability of head and neck squamous cell carcinoma cells producing mutated forms of CTNNA2 and CTNNA3 or in cells where both α-catenins are silenced. Analysis of the clinical relevance of these mutations demonstrates that they are associated with poor prognosis. We conclude that CTNNA2 and CTNNA3 are tumour suppressor genes frequently mutated in laryngeal carcinomas.

The mitochondrial quality control system is essential for the preservation and regulation of mitochondrial function. This system is formed by a complex machinery that controls and maintains protein function and regulates mitochondrial morphology through a coordinated system of continual fusion and fission events. Impairments in the mitochondrial quality control system through either mutation or deficiency in any of its components, can lead to mitochondrial dysfunction. However, the physiological consequences of these deficiencies remain unknown in most cases. Here, we briefly review the role of the OPA1-OMA1 system in mitochondrial biology, and summarize our recent report on the generation and phenotypic characterization of a model deficient in OMA1, an ATP-independent mitochondrial metalloprotease that participates in mitochondrial quality control. Interestingly, Oma1-deficient mice display an obesity phenotype, characterized by hepatic steatosis, decrease in energy expenditure and defective thermogenic regulation. In addition, our study has provided in vivo evidence of OMA1 function as a mitochondrial quality control protease, inactivating OPA1 under stress conditions and inhibiting mitochondrial fusion. Further, we have demonstrated the essential role of the OMA1-OPA1 system for brown adipose function and how this system regulates metabolic homeostasis in mice.

We demonstrate coherent control of a quantum dot exciton using photocurrent detection with a sinusoidal reverse bias. Optical control is performed at low bias, where tunneling-limited coherence times are long. Following this step, the tunneling rates are increased to remove the long-lived hole, achieving a high photocurrent signal. For a detection efficiency of 68%, electron and hole tunneling times during optical control of 200 ps and 20 ns can be achieved, compared to 120 ps and 7 ns for the constant bias case, respectively., Comment: 11 pages, 5 figures

The electron–phonon coupling in self-assembled InGaAs quantum dots is relatively weak at low light intensities, which means that the zero-phonon line in emission is strong compared to the phonon sideband. However, the coupling to acoustic phonons can be dynamically enhanced in the presence of an intense optical pulse tuned within the phonon sideband. Recent experiments have shown that this dynamic vibronic coupling can enable population inversion to be achieved when pumping with a blueshifted laser and for rapid de-excitation of an inverted state with red detuning. In this paper we confirm the incoherent nature of the phonon-assisted pumping process and explore the temperature dependence of the mechanism. We also show that a combination of blueshifted and redshifted pulses can create and destroy an exciton within a timescale of ∼20 ps as determined by the pulse duration and ultimately limited by the phonon thermalization time.

Frequent somatic mutations in components of the RNA processing machinery in chronic lymphocytic leukemia